PolyADP-ribose is a polymer that is associated with the chromatin of eukaryotic cells. It is formed from NAD and has been shown to inhibit the capacity of nuclear DNA to function as a template for DNA polymerase. In neoplastic cells, NAD levels are known to be depressed. Because polyADP-ribose is formed from NAD and is involved in the regulation of DNA-replication, a relationship should exist between the low levels of NAD in tumors and their property of continuous proliferation. Intracellular levels of NAD appear to play an important role in the control of cell proliferation. However, little is known concerning the regulation of NAD levels in tissues. The information presently available suggests that intracellular NAD is controlled by the enzyme NAD glycohydrolase, which acts by hydrolyzing excess NAD. In the research that is proposed, the relationships between NAD, polyADP- ribose, polyADP-ribose polymerase, NAD glycohydrolase, and cell proliferation will be explored. Because normal and malignant cells are expected to differ widely with regard to these biochemical parameters, both normal and leukemic human leukocytes will be examined, using microtechniques where necessary. Included in the study will be freshly- drawn leukocytes, leukocytes that have been cultured under short-term conditions, and leukocytes that have become established in long-term tissue culture. Cytogenetic analysis will be performed on all cell types in order to determine whether abnormalities in chromosome number or morphology are correlated with the various biochemical parameters studied.